Adiponectin in chronic heart failure: influence of diabetes and genetic variants

Serge Masson; Francesca Gori; Roberto Latini; Valentina Milani; Allan Flyvbjerg; Jan Frystyk; Luisa Crociati; Silvia Pietri; Tarcisio Vago; Simona Barlera; Aldo P Maggioni; Gianni Tognoni; Luigi Tavazzi; Torbjørn Omland; Maria Grazia Franzosi; GISSI-HF Investigators

doi:10.1111/j.1365-2362.2011.02548.x

Adiponectin in chronic heart failure: influence of diabetes and genetic variants

Serge Masson, Francesca Gori, Roberto Latini, Valentina Milani, Allan Flyvbjerg, Jan Frystyk, Luisa Crociati, Silvia Pietri, Tarcisio Vago, Simona Barlera, Aldo P Maggioni, Gianni Tognoni, Luigi Tavazzi, Torbjørn Omland, Maria Grazia Franzosi, GISSI-HF Investigators

17 Citationer (Scopus)

Abstract

BACKGROUND: We hypothesized that, besides type 2 diabetes (T2D) and body mass index (BMI), circulating adiponectin concentration would be associated with variants of the ADIPOQ gene in patients with chronic heart failure (CHF). We also assessed the influence of these confounders on the prognostic value of adiponectin.

METHODS: Plasma adiponectin was measured at entry and after 3 months in approximately 1200 patients with CHF enrolled in the GISSI-HF trial. Four common single-nucleotide polymorphisms (SNPs) spanning the ADIPOQ gene were studied: rs17300539 (-11391G→A), rs266729 (-11377C→G), rs2241766 (+45T→G) and rs1501299 (+276G→T). Associations with clinical characteristics and mortality were evaluated in patients with or without T2D.

RESULTS: Adiponectin concentrations were negatively related to BMI, higher in women and older persons, but lower in patients with diabetes. T-allele carriers for rs1501299 and A-allele carriers for rs17300539 had significantly elevated adiponectin concentrations. Irrespective of diabetes, baseline plasma adiponectin was independently associated with mortality (adjusted HR [95%CI] per 1 SD increase in adiponectin concentration = 1·24[1·12-1·37], P < 0·0001) and improved prognostic discrimination beyond clinical risk factors (integrated discrimination improvement, P = 0·005). Patients with increasing adiponectin concentration over 3 months had worse outcome than those with stable levels (unadjusted HR = 1·46[1·09-1·96], P = 0·01); this relation was attenuated by the genetic variants examined and by robust confounders like age, diabetes, BMI or NT-proBNP (adjusted HR = 1·37[0·97-1·94], P = 0·075).

CONCLUSIONS: Although diabetes and genetic variants at the ADIPOQ gene influence the circulating levels of adiponectin in CHF, higher plasma adipokine levels, but not genetic variants, are consistently associated with a poor prognosis.

Originalsprog	Engelsk
Tidsskrift	European Journal of Clinical Investigation
Vol/bind	41
Udgave nummer	12
Sider (fra-til)	1330-8
Antal sider	9
ISSN	0014-2972
DOI	https://doi.org/10.1111/j.1365-2362.2011.02548.x
Status	Udgivet - dec. 2011
Udgivet eksternt	Ja

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10.1111/j.1365-2362.2011.02548.x

Citationsformater

Masson, S., Gori, F., Latini, R., Milani, V., Flyvbjerg, A., Frystyk, J., Crociati, L., Pietri, S., Vago, T., Barlera, S., Maggioni, A. P., Tognoni, G., Tavazzi, L., Omland, T., Franzosi, M. G., & GISSI-HF Investigators (2011). Adiponectin in chronic heart failure: influence of diabetes and genetic variants. European Journal of Clinical Investigation, 41(12), 1330-8. https://doi.org/10.1111/j.1365-2362.2011.02548.x

Masson, S, Gori, F, Latini, R, Milani, V, Flyvbjerg, A, Frystyk, J, Crociati, L, Pietri, S, Vago, T, Barlera, S, Maggioni, AP, Tognoni, G, Tavazzi, L, Omland, T, Franzosi, MG & GISSI-HF Investigators 2011, 'Adiponectin in chronic heart failure: influence of diabetes and genetic variants', European Journal of Clinical Investigation, bind 41, nr. 12, s. 1330-8. https://doi.org/10.1111/j.1365-2362.2011.02548.x

@article{40edd21b6a9e41c2965bcc51b58b98c7,

title = "Adiponectin in chronic heart failure: influence of diabetes and genetic variants",

abstract = "BACKGROUND: We hypothesized that, besides type 2 diabetes (T2D) and body mass index (BMI), circulating adiponectin concentration would be associated with variants of the ADIPOQ gene in patients with chronic heart failure (CHF). We also assessed the influence of these confounders on the prognostic value of adiponectin.METHODS: Plasma adiponectin was measured at entry and after 3 months in approximately 1200 patients with CHF enrolled in the GISSI-HF trial. Four common single-nucleotide polymorphisms (SNPs) spanning the ADIPOQ gene were studied: rs17300539 (-11391G→A), rs266729 (-11377C→G), rs2241766 (+45T→G) and rs1501299 (+276G→T). Associations with clinical characteristics and mortality were evaluated in patients with or without T2D.RESULTS: Adiponectin concentrations were negatively related to BMI, higher in women and older persons, but lower in patients with diabetes. T-allele carriers for rs1501299 and A-allele carriers for rs17300539 had significantly elevated adiponectin concentrations. Irrespective of diabetes, baseline plasma adiponectin was independently associated with mortality (adjusted HR [95%CI] per 1 SD increase in adiponectin concentration = 1·24[1·12-1·37], P < 0·0001) and improved prognostic discrimination beyond clinical risk factors (integrated discrimination improvement, P = 0·005). Patients with increasing adiponectin concentration over 3 months had worse outcome than those with stable levels (unadjusted HR = 1·46[1·09-1·96], P = 0·01); this relation was attenuated by the genetic variants examined and by robust confounders like age, diabetes, BMI or NT-proBNP (adjusted HR = 1·37[0·97-1·94], P = 0·075).CONCLUSIONS: Although diabetes and genetic variants at the ADIPOQ gene influence the circulating levels of adiponectin in CHF, higher plasma adipokine levels, but not genetic variants, are consistently associated with a poor prognosis.",

keywords = "Adiponectin, Age Factors, Aged, Aged, 80 and over, Body Mass Index, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Heart Failure, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Sex Factors, Survival Analysis, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",

author = "Serge Masson and Francesca Gori and Roberto Latini and Valentina Milani and Allan Flyvbjerg and Jan Frystyk and Luisa Crociati and Silvia Pietri and Tarcisio Vago and Simona Barlera and Maggioni, {Aldo P} and Gianni Tognoni and Luigi Tavazzi and Torbj{\o}rn Omland and Franzosi, {Maria Grazia} and {GISSI-HF Investigators}",

note = "{\textcopyright} 2011 The Authors. European Journal of Clinical Investigation {\textcopyright} 2011 Stichting European Society for Clinical Investigation Journal Foundation.",

year = "2011",

month = dec,

doi = "10.1111/j.1365-2362.2011.02548.x",

language = "English",

volume = "41",

pages = "1330--8",

journal = "European Journal of Clinical Investigation",

issn = "0014-2972",

publisher = "John Wiley and Sons Inc.",

number = "12",

}

TY - JOUR

T1 - Adiponectin in chronic heart failure

T2 - influence of diabetes and genetic variants

AU - Masson, Serge

AU - Gori, Francesca

AU - Latini, Roberto

AU - Milani, Valentina

AU - Flyvbjerg, Allan

AU - Frystyk, Jan

AU - Crociati, Luisa

AU - Pietri, Silvia

AU - Vago, Tarcisio

AU - Barlera, Simona

AU - Maggioni, Aldo P

AU - Tognoni, Gianni

AU - Tavazzi, Luigi

AU - Omland, Torbjørn

AU - Franzosi, Maria Grazia

AU - GISSI-HF Investigators

PY - 2011/12

Y1 - 2011/12

N2 - BACKGROUND: We hypothesized that, besides type 2 diabetes (T2D) and body mass index (BMI), circulating adiponectin concentration would be associated with variants of the ADIPOQ gene in patients with chronic heart failure (CHF). We also assessed the influence of these confounders on the prognostic value of adiponectin.METHODS: Plasma adiponectin was measured at entry and after 3 months in approximately 1200 patients with CHF enrolled in the GISSI-HF trial. Four common single-nucleotide polymorphisms (SNPs) spanning the ADIPOQ gene were studied: rs17300539 (-11391G→A), rs266729 (-11377C→G), rs2241766 (+45T→G) and rs1501299 (+276G→T). Associations with clinical characteristics and mortality were evaluated in patients with or without T2D.RESULTS: Adiponectin concentrations were negatively related to BMI, higher in women and older persons, but lower in patients with diabetes. T-allele carriers for rs1501299 and A-allele carriers for rs17300539 had significantly elevated adiponectin concentrations. Irrespective of diabetes, baseline plasma adiponectin was independently associated with mortality (adjusted HR [95%CI] per 1 SD increase in adiponectin concentration = 1·24[1·12-1·37], P < 0·0001) and improved prognostic discrimination beyond clinical risk factors (integrated discrimination improvement, P = 0·005). Patients with increasing adiponectin concentration over 3 months had worse outcome than those with stable levels (unadjusted HR = 1·46[1·09-1·96], P = 0·01); this relation was attenuated by the genetic variants examined and by robust confounders like age, diabetes, BMI or NT-proBNP (adjusted HR = 1·37[0·97-1·94], P = 0·075).CONCLUSIONS: Although diabetes and genetic variants at the ADIPOQ gene influence the circulating levels of adiponectin in CHF, higher plasma adipokine levels, but not genetic variants, are consistently associated with a poor prognosis.

AB - BACKGROUND: We hypothesized that, besides type 2 diabetes (T2D) and body mass index (BMI), circulating adiponectin concentration would be associated with variants of the ADIPOQ gene in patients with chronic heart failure (CHF). We also assessed the influence of these confounders on the prognostic value of adiponectin.METHODS: Plasma adiponectin was measured at entry and after 3 months in approximately 1200 patients with CHF enrolled in the GISSI-HF trial. Four common single-nucleotide polymorphisms (SNPs) spanning the ADIPOQ gene were studied: rs17300539 (-11391G→A), rs266729 (-11377C→G), rs2241766 (+45T→G) and rs1501299 (+276G→T). Associations with clinical characteristics and mortality were evaluated in patients with or without T2D.RESULTS: Adiponectin concentrations were negatively related to BMI, higher in women and older persons, but lower in patients with diabetes. T-allele carriers for rs1501299 and A-allele carriers for rs17300539 had significantly elevated adiponectin concentrations. Irrespective of diabetes, baseline plasma adiponectin was independently associated with mortality (adjusted HR [95%CI] per 1 SD increase in adiponectin concentration = 1·24[1·12-1·37], P < 0·0001) and improved prognostic discrimination beyond clinical risk factors (integrated discrimination improvement, P = 0·005). Patients with increasing adiponectin concentration over 3 months had worse outcome than those with stable levels (unadjusted HR = 1·46[1·09-1·96], P = 0·01); this relation was attenuated by the genetic variants examined and by robust confounders like age, diabetes, BMI or NT-proBNP (adjusted HR = 1·37[0·97-1·94], P = 0·075).CONCLUSIONS: Although diabetes and genetic variants at the ADIPOQ gene influence the circulating levels of adiponectin in CHF, higher plasma adipokine levels, but not genetic variants, are consistently associated with a poor prognosis.

KW - Adiponectin

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Body Mass Index

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Genetic Predisposition to Disease

KW - Heart Failure

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

KW - Sex Factors

KW - Survival Analysis

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/j.1365-2362.2011.02548.x

DO - 10.1111/j.1365-2362.2011.02548.x

M3 - Journal article

C2 - 21623778

SN - 0014-2972

VL - 41

SP - 1330

EP - 1338

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

IS - 12

ER -

Adiponectin in chronic heart failure: influence of diabetes and genetic variants

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